For antibiotic resistance, treat cystic fibrosis with nanoparticles

Cystic fibrosis: overcome antibiotic resistance by nanoparticles

Cystic fibrosis is a congenital metabolic disease. In Germany alone, around 8,000 people suffer from the incurable disease, especially children and young adults. Infections of the respiratory tract are among the most common sequelae. Researchers have now succeeded in developing a method to treat the often deadly respiratory infections. The focus is on nanoparticles that better bring antibiotics to their destination.

Around 8,000 cystic fibrosis patients in Germany

According to health experts, up to 8,000 patients with cystic fibrosis live in this country. About one in every 3,300 children is born in Germany annually with the previously incurable metabolic disease. Early diagnosis and early therapy can help to significantly improve the quality of life and life expectancy of cystic fibrosis patients. To achieve this, the metabolic disease study has been integrated into neonatal screening. Especially children with cystic fibrosis can often be treated well. Physicians and pharmacists at the University of Jena combat cystic fibrosis with nanoparticles.

Researchers have succeeded in developing an efficient way to treat the often deadly respiratory infections that people with cystic fibrosis suffer from. The focus is on nanoparticles that better bring antibiotics to their destination. (Image: Zerbor / fotolia.com)

Self-cleaning function of the lung is disturbed

In cystic fibrosis (also called cystic fibrosis, CF), a channel protein on the cell surface is disturbed by mutations.

This reduces the water content of various secretions in the body - it creates a tough mucus, reports the Friedrich Schiller University Jena in a message that was published by the Information Service Science (idw).

Dysfunction of internal organs are the result. In addition, the mucus sets the airways. This not only disturbs the self-cleaning function of the lungs, but it also colonizes the mucus with bacteria.

As a result, chronic infections arise. The lung is severely damaged, which often leads to the death of the patient or requires a transplant.

The average life expectancy of sufferers today is about 40 years thanks to medical progress.

A major part of this is due to long-term treatments with inhaled antibiotics, which do not prevent bacterial colonization but at least keep it in check for a longer period of time.

However, the bacteria defend themselves by resistance development and the formation of so-called biofilms in and under the mucus layer, which shield the bacteria in the lower rows like a protective shield.

Complicated way to the pathogens

Researchers at Friedrich Schiller University Jena have now succeeded in developing a much more efficient method for treating the often deadly respiratory infections. The focus is on nanoparticles that better bring antibiotics to their destination.

"As a rule, the drugs enter the body through inhalation and then travel a complicated path back to the pathogens, where many are left behind," explains Prof. Dr. med. Dagmar Fischer from the Department of Pharmaceutical Technology of the University of Jena, who together with her colleague Prof. Dr. med. Mathias Pletz from the Center for Infection Medicine and Hospital Hygiene at the University Hospital Jena.

The drug particles must first have a certain size to get into the deeper airways and not previously rip off somewhere.

Finally, they must penetrate both the thick mucus layer on the respiratory tract and the lower layers of bacterial biofilm.

Nanoparticles reach their destination more easily

To overcome the concentrated resistance, the researchers encapsulated active ingredients, such as the antibiotic tobramycin, in a polyester polymer.

They tested the resulting nanoparticles in the laboratory, where they had previously simulated the existing lung situation - both in the static and in the dynamic state, ie with simulated flow movements.

For this purpose, Pletz 'group has developed new test systems that can better represent the situation in the lungs.

The scientists found that their nanoparticles through the sponge-like network of the mucus layer is easier than the pure drug and finally kill easily the pathogens.

An additionally applied envelope made of polyethylene glycol also makes it almost invisible to the immune system. "All materials of the nanocarrier are also biocompatible, biodegradable, non-toxic and therefore harmless to humans," informs Fischer.

Give an antibiotic its effect

The scientists from Jena do not know exactly why their nanoparticles fight bacteria so much more effectively. But they want to finally uncover that in the coming year.

"We have two assumptions: Either the much more efficient transport method promotes significantly more active substance to the infection or the nanoparticles overcomes a defense mechanism that the bacterium has developed against the antibiotic," said the Jena pharmacist.

"The latter would mean that we were able to use a nanoparticle to restore the effect of an antibiotic that he had actually lost by resistance formation of the bacteria."

"Specifically, we suspect that bacteria from the lower layers of the biofilm fall into a kind of winter rigidity and absorb hardly any substances from outside. At this stage, they are invulnerable to most antibiotics that kill only dividing bacteria. The nanoparticles transport the antibiotics almost against the will of the bacteria into the cell interior, where they can unfold their effect, "adds Mathias Pletz.

Combat respiratory infections more effectively in cystic fibrosis patients

In addition, the Jena research team still has to prepare the nanoparticles for inhalation. Because at 200 nanometers, the particle is too small to reach the deeper respiratory tract.

"The respiratory system filters out particles that are too large or too small," explains Fischer. "We therefore have a preferred window between one and five microns." Also for this problem, the Jena researchers already have promising solution ideas.

Based on the research results available at the time, the Jena research team is convinced that it has found an extremely promising method for more efficiently combating respiratory infections in cystic fibrosis patients and thus potentially contributing to a longer life expectancy for the patients.

"We were able to show that nanoparticle packaging increases the effectiveness of antibiotics against biofilms by a factor of 1,000," says the infectious scientist. (Ad)